Periods
Different time periods are specified for the analysis:
- The data extraction period: Data extraction is foreseen from the first date of a documented SARS-CoV-2 infection in the population until the most recent date at which data is available at the time of analysis. All individuals vaccinated with at least one dose of the SARS-CoV-2 vaccine (any of the available brands) and all individuals eligible to be vaccinated with a documented positive diagnosis (irrespective of the type of test) for SARS-CoV-2 infection during the data extraction period are included in the study population.
- The enrollment period: A sequence of nested (daily) trials are emulated with increasing time (t1, t2, …, tn), iterating over the days in the enrollment period. At each eligible time during the enrollment period, the vaccination status of eligible individuals is assessed and every individual who has completed a primary vaccination schedule at that time (coded here as initiation of the intervention strategy when emulating a nested target trial) is matched to an individual who has not (yet) completed the primary vaccination schedule (coded here as the control strategy when emulating a nested target trial).
- The study period: The study period is considered from the start of the enrollment period until one year after the end of the enrollment period, to allow a minimal possible follow-up period of one year.
| Period | Time range |
|---|---|
| Data extraction period | 2020-03-05 - 2022-05-19 |
| Enrollment period | 2021-01-01 - 2021-08-30 |
| Study period | 2021-01-01 - 2022-08-30 |
Study population and enrollment
A flow diagram displaying the process of obtaining a matched study population considered for survival analysis.
Description of the study population: table 1
| Completed a primary vaccination schedule during the enrollment period (N=7757) |
Not completed a primary vaccination schedule during the enrollment period (N=1126) |
P-value | |
|---|---|---|---|
ᵃ5-year age groups | |||
| sex_cd | |||
| 0 | 136 (1.8%) | 12 (1.1%) | 0.0294 |
| 1 | 3663 (47.2%) | 572 (50.8%) | |
| 2 | 3958 (51.0%) | 542 (48.1%) | |
| age_cdᵃ | |||
| 10 | 905 (11.7%) | 137 (12.2%) | 0.73 |
| 11 | 1016 (13.1%) | 133 (11.8%) | |
| 12 | 992 (12.8%) | 158 (14.0%) | |
| 13 | 865 (11.2%) | 112 (9.9%) | |
| 14 | 743 (9.6%) | 107 (9.5%) | |
| 15 | 528 (6.8%) | 83 (7.4%) | |
| 16 | 348 (4.5%) | 49 (4.4%) | |
| 17 | 199 (2.6%) | 25 (2.2%) | |
| 18 | 179 (2.3%) | 27 (2.4%) | |
| 2 | 14 (0.2%) | 1 (0.1%) | |
| 3 | 19 (0.2%) | 0 (0%) | |
| 4 | 56 (0.7%) | 7 (0.6%) | |
| 5 | 102 (1.3%) | 13 (1.2%) | |
| 6 | 211 (2.7%) | 24 (2.1%) | |
| 7 | 344 (4.4%) | 49 (4.4%) | |
| 8 | 494 (6.4%) | 83 (7.4%) | |
| 9 | 742 (9.6%) | 118 (10.5%) | |
| residence_area_cd | |||
| 731 | 1211 (15.6%) | 165 (14.7%) | 0.708 |
| 732 | 1164 (15.0%) | 171 (15.2%) | |
| 733 | 5382 (69.4%) | 790 (70.2%) | |
| pregnancy_bl | |||
| Yes | 194 (2.5%) | 42 (3.7%) | 0.0216 |
| No | 7563 (97.5%) | 1084 (96.3%) | |
| institutionalized_bl | |||
| Yes | 255 (3.3%) | 20 (1.8%) | 0.00917 |
| No | 6657 (85.8%) | 974 (86.5%) | |
| Missing | 845 (10.9%) | 132 (11.7%) | |
| foreign_bl | |||
| Yes | 1154 (14.9%) | 153 (13.6%) | 0.273 |
| No | 6603 (85.1%) | 973 (86.4%) | |
| socecon_lvl_cd | |||
| 1 | 175 (2.3%) | 23 (2.0%) | 0.173 |
| 2 | 1069 (13.8%) | 137 (12.2%) | |
| 3 | 2791 (36.0%) | 425 (37.7%) | |
| 4 | 2682 (34.6%) | 369 (32.8%) | |
| 5 | 1040 (13.4%) | 172 (15.3%) | |
| comorbidities_bl | |||
| Yes | 3887 (50.1%) | 549 (48.8%) | 0.414 |
| No | 3870 (49.9%) | 577 (51.2%) | |
| immunestatus_bl | |||
| Yes | 2154 (27.8%) | 295 (26.2%) | 0.287 |
| No | 5603 (72.2%) | 831 (73.8%) | |
| Intervention group (N=7757) |
Control group (N=7757) |
P-value | |
|---|---|---|---|
ᵃ5-year age groups | |||
| sex_cd | |||
| 0 | 136 (1.8%) | 70 (0.9%) | <0.001 |
| 1 | 3663 (47.2%) | 3851 (49.6%) | |
| 2 | 3958 (51.0%) | 3836 (49.5%) | |
| age_cdᵃ | |||
| 10 | 905 (11.7%) | 1011 (13.0%) | <0.001 |
| 11 | 1016 (13.1%) | 1076 (13.9%) | |
| 12 | 992 (12.8%) | 1056 (13.6%) | |
| 13 | 865 (11.2%) | 873 (11.3%) | |
| 14 | 743 (9.6%) | 745 (9.6%) | |
| 15 | 528 (6.8%) | 517 (6.7%) | |
| 16 | 348 (4.5%) | 324 (4.2%) | |
| 17 | 199 (2.6%) | 153 (2.0%) | |
| 18 | 179 (2.3%) | 150 (1.9%) | |
| 2 | 14 (0.2%) | 4 (0.1%) | |
| 3 | 19 (0.2%) | 10 (0.1%) | |
| 4 | 56 (0.7%) | 34 (0.4%) | |
| 5 | 102 (1.3%) | 72 (0.9%) | |
| 6 | 211 (2.7%) | 165 (2.1%) | |
| 7 | 344 (4.4%) | 316 (4.1%) | |
| 8 | 494 (6.4%) | 499 (6.4%) | |
| 9 | 742 (9.6%) | 752 (9.7%) | |
| residence_area_cd | |||
| 731 | 1211 (15.6%) | 1153 (14.9%) | 0.27 |
| 732 | 1164 (15.0%) | 1132 (14.6%) | |
| 733 | 5382 (69.4%) | 5472 (70.5%) | |
| pregnancy_bl | |||
| Yes | 194 (2.5%) | 149 (1.9%) | 0.0163 |
| No | 7563 (97.5%) | 7608 (98.1%) | |
| institutionalized_bl | |||
| Yes | 292 (3.8%) | 243 (3.1%) | 0.0347 |
| No | 7465 (96.2%) | 7514 (96.9%) | |
| foreign_bl | |||
| Yes | 1154 (14.9%) | 1097 (14.1%) | 0.202 |
| No | 6603 (85.1%) | 6660 (85.9%) | |
| socecon_lvl_cd | |||
| 1 | 175 (2.3%) | 82 (1.1%) | <0.001 |
| 2 | 1069 (13.8%) | 1037 (13.4%) | |
| 3 | 2791 (36.0%) | 2921 (37.7%) | |
| 4 | 2682 (34.6%) | 2762 (35.6%) | |
| 5 | 1040 (13.4%) | 955 (12.3%) | |
| comorbidities_bl | |||
| Yes | 3887 (50.1%) | 3891 (50.2%) | 0.962 |
| No | 3870 (49.9%) | 3866 (49.8%) | |
| immunestatus_bl | |||
| Yes | 2154 (27.8%) | 2154 (27.8%) | 1 |
| No | 5603 (72.2%) | 5603 (72.2%) | |
Two-by-two tables
The individuals in the imported dataset are counted by whether they were fully vaccinated within the enrollment period and whether they experienced a known/confirmed infection (confirmed_case_bl, see CDM for definition).
| Confirmed case | No confirmed case | Total | |
|---|---|---|---|
| Completed a primary vaccination schedule during the enrollment period | 2947 | 5801 | 8748 |
| Didn’t complete a primary vaccination schedule during the enrollment period | 394 | 858 | 1252 |
| Total | 3341 | 6659 | 10000 |
Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 1.0704822
The individuals eligible for analysis are counted by whether they were fully vaccinated within the enrollment period and whether they experienced a known/confirmed infection (confirmed_case_bl, see CDM for definition).
| Confirmed case | No confirmed case | Total | |
|---|---|---|---|
| Completed a primary vaccination schedule during the enrollment period | 2478 | 5279 | 7757 |
| Didn’t complete a primary vaccination schedule during the enrollment period | 330 | 796 | 1126 |
| Total | 2808 | 6075 | 8883 |
Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 1.0900137
The matched individuals are counted by intervention group and whether they experienced a known/confirmed infection (confirmed_case_bl, see CDM for definition).
| Confirmed case | No confirmed case | Total | |
|---|---|---|---|
| Intervention group | 2478 | 5279 | 7757 |
| Control group | 2039 | 5718 | 7757 |
| Total | 4517 | 10997 | 15514 |
Ratio = \(\frac{(\frac{confirmed \ cases}{primary vaccinated \ individuals})} {(\frac{confirmed \ cases}{not-primary vaccinated \ individuals})}\) = 1.2153016
Survival in un-matched population
| Variable | Beta (SE) | HR (95% CI) | P |
|---|---|---|---|
| fully_vaccinated_bl_bisTRUE | 0.01 (0.07) | 1.01 (0.88, 1.15) | 0.93 |
| Strata | Time | Number at risk | Cumulative sum of number of events | Cumulative sum of number censored | Survival | Std. error | Cumulative hazard | Std. error cumulative hazard |
|---|---|---|---|---|---|---|---|---|
|
|
0 | 1093 | 0 | 0 | 1.0000000 | 0.0000000000 | 0.0000000000 | 0.0000000000 |
|
|
1 | 1093 | 0 | 0 | 1.0000000 | 0.0000000000 | 0.0000000000 | 0.0000000000 |
|
|
100 | 1064 | 29 | 0 | 0.9734675 | 0.0048611561 | 0.0268748938 | 0.0049906903 |
|
|
200 | 944 | 60 | 89 | 0.9447488 | 0.0069354617 | 0.0567982438 | 0.0073361433 |
|
|
300 | 910 | 72 | 111 | 0.9324909 | 0.0076954581 | 0.0698496564 | 0.0082471116 |
|
|
400 | 690 | 235 | 172 | 0.7568874 | 0.0138971237 | 0.2781052564 | 0.0183305791 |
|
|
500 | 638 | 283 | 172 | 0.7039273 | 0.0148792711 | 0.3505367292 | 0.0211035233 |
|
|
600 | 638 | 283 | 172 | 0.7039273 | 0.0148792711 | 0.3505367292 | 0.0211035233 |
|
|
0 | 7757 | 283 | 172 | 1.0000000 | 0.0000000000 | 0.0000000000 | 0.0000000000 |
|
|
1 | 7757 | 284 | 172 | 0.9998711 | 0.0001289075 | 0.0001289158 | 0.0001289158 |
|
|
100 | 7653 | 388 | 172 | 0.9864638 | 0.0013120230 | 0.0136268117 | 0.0013298507 |
|
|
200 | 3642 | 815 | 3833 | 0.9184806 | 0.0034924050 | 0.0849954454 | 0.0038004224 |
|
|
300 | 2516 | 1266 | 4432 | 0.7799519 | 0.0067093405 | 0.2483253662 | 0.0085946669 |
|
|
400 | 2232 | 1399 | 4593 | 0.7386179 | 0.0072482648 | 0.3027433080 | 0.0098052406 |
|
|
500 | 756 | 1400 | 6073 | 0.7382516 | 0.0072539232 | 0.3032393397 | 0.0098177794 |
|
|
600 | 2 | 1400 | 6810 | 0.7382516 | 0.0072539232 | 0.3032393397 | 0.0098177794 |
| Variable | Beta (SE) | HR (95% CI) | P |
|---|---|---|---|
| fully_vaccinated_bl_bisTRUE | -0.03 (0.07) | 0.97 (0.85, 1.12) | 0.70 |
| sex_cd | |||
| 1 (ref) | – | – | – |
| 2 | 0.01 (0.06) | 1.01 (0.90, 1.14) | 0.80 |
| 0 | 0.27 (0.20) | 1.31 (0.89, 1.95) | 0.18 |
| age_cd | |||
| 2 (ref) | – | – | – |
| 3 | -1.37 (1.23) | 0.25 (0.02, 2.81) | 0.26 |
| 4 | -0.42 (0.78) | 0.65 (0.14, 3.04) | 0.59 |
| 5 | 0.11 (0.74) | 1.12 (0.26, 4.79) | 0.88 |
| 6 | -0.17 (0.73) | 0.85 (0.20, 3.54) | 0.82 |
| 7 | -0.29 (0.72) | 0.75 (0.18, 3.08) | 0.69 |
| 8 | -0.12 (0.72) | 0.89 (0.22, 3.61) | 0.87 |
| 9 | -0.32 (0.71) | 0.72 (0.18, 2.93) | 0.65 |
| 10 | -0.20 (0.71) | 0.82 (0.20, 3.29) | 0.77 |
| 11 | -0.15 (0.71) | 0.86 (0.21, 3.48) | 0.84 |
| 12 | -0.38 (0.71) | 0.69 (0.17, 2.77) | 0.60 |
| 13 | -0.24 (0.71) | 0.78 (0.19, 3.17) | 0.73 |
| 14 | -0.27 (0.71) | 0.76 (0.19, 3.09) | 0.70 |
| 15 | -0.21 (0.72) | 0.81 (0.20, 3.28) | 0.76 |
| 16 | -0.27 (0.72) | 0.76 (0.19, 3.14) | 0.71 |
| 17 | -0.22 (0.73) | 0.80 (0.19, 3.36) | 0.76 |
| 18 | -0.41 (0.74) | 0.66 (0.16, 2.80) | 0.58 |
| residence_area_cd | |||
| 731 (ref) | – | – | – |
| 732 | -0.11 (0.10) | 0.90 (0.73, 1.10) | 0.31 |
| 733 | -0.05 (0.08) | 0.95 (0.81, 1.11) | 0.52 |
| pregnancy_blTRUE | 0.10 (0.17) | 1.10 (0.79, 1.52) | 0.57 |
| institutionalized_blTRUE | 0.01 (0.16) | 1.01 (0.74, 1.38) | 0.95 |
| foreign_blTRUE | -0.02 (0.08) | 0.98 (0.84, 1.15) | 0.84 |
| socecon_lvl_cd | |||
| 1 (ref) | – | – | – |
| 2 | -0.04 (0.21) | 0.96 (0.64, 1.44) | 0.85 |
| 3 | -0.09 (0.20) | 0.91 (0.62, 1.35) | 0.65 |
| 4 | -0.07 (0.20) | 0.94 (0.63, 1.38) | 0.74 |
| 5 | -0.01 (0.21) | 0.99 (0.66, 1.49) | 0.98 |
| comorbidities_blTRUE | 0.03 (0.06) | 1.03 (0.93, 1.16) | 0.55 |
| immunestatus_blTRUE | -0.06 (0.06) | 0.94 (0.83, 1.07) | 0.35 |